Efficient methods for solid phase synthesis using trityl chloride resins

Abstract

Disclosed are efficient methods for loading amino derivatives onto trityl chloride resins and for cleaving chemically modified amino derivatives from trityl chloride resins. Methods for making a library of discrete chemically modified amino derivatives also disclosed.

1. A method for loading acid-containing arylamines onto trityl chloride resins, wherein said method comprises:
 (a) obtaining activated-ester-containing arylamines comprising an acid moiety that is protected from reacting with a trityl group and activated for subsequent modification, wherein said activated-ester-containing arylamines comprise an unblocked amino group, and 
 (b) using diisopropylethylamine in methylene chloride to load said activated ester-containing arylamines onto said trityl chloride resins through an amino group of said activated ester-containing arylamines. 
 
     
     
       2. The method of  claim 1 , wherein said acid-containing arylamine is an aminobenzoie acid derivative. 
     
     
       3. The method of  claim 2 , wherein the derivative is an activated 2,5-dioxo-pyrrolidin-1-yl ester. 
     
     
       4. The method of  claim 2 , wherein the derivative is an activated pentafluorophenyl ester. 
     
     
       5. A method to produce a library of modified acid-containing arylamines, comprising:
 a) using diisopropylethylamine in methylene chloride to load an activated-ester-containing arylamine onto a trityl chloride resin through an amino group of said activated-ester-containing arylamine, wherein an acid moiety of said activated-ester-containing arylamine is blocked and activated using N-hydroxysuccinimide or pentafluorophenyl ester, and wherein said activated-ester-containing arylamine comprises an unblocked amino group; 
 b) chemically modifying said loaded acid-containing arylamine; and 
 c) cleaving said chemically modified acid-containing arylamine from said trityl chloride resin using an acetic acid containing solution.